The Association of Lipoprotein(a) and Circulating Monocyte Subsets with Severe Coronary Atherosclerosis

Abstract

Background and aims: Chronic inflammation associated with the uncontrolled activation of innate and acquired immunity plays a fundamental role in all stages of atherogenesis. Monocytes are a heterogeneous population and each subset contributes differently to the inflammatory process. A high level of lipoprotein(a) (Lp(a)) is a proven cardiovascular risk factor. The aim of the study was to investigate the association between the increased concentration of Lp(a) and monocyte subpopulations in patients with a different severity of coronary atherosclerosis. Methods: 150 patients (124 males) with a median age of 60 years undergoing a coronary angiography were enrolled. Lipids, Lp(a), autoantibodies, blood cell counts and monocyte subpopulations (classical, intermediate, non-classical) were analyzed. Results: The patients were divided into two groups depending on the Lp(a) concentration: normal Lp(a) < 30 mg/dL (n = 82) and hyperLp(a) ≥ 30 mg/dL (n = 68). Patients of both groups were comparable by risk factors, autoantibody levels and blood cell counts. In patients with hyperlipoproteinemia(a) the content (absolute and relative) of non-classical monocytes was higher (71.0 (56.6; 105.7) vs. 62.2 (45.7; 82.4) 103/mL and 17.7 (13.0; 23.3) vs. 15.1 (11.4; 19.4) %, respectively, p < 0.05). The association of the relative content of non-classical monocytes with the Lp(a) concentration retained a statistical significance when adjusted for gender and age (r = 0.18, p = 0.03). The severity of coronary atherosclerosis was associated with the Lp(a) concentration as well as the relative and absolute (p < 0.05) content of classical monocytes. The high content of non-classical monocytes (OR = 3.5, 95% CI 1.2–10.8) as well as intermediate monocytes (OR = 8.7, 2.5–30.6) in patients with hyperlipoproteinemia(a) were associated with triple-vessel coronary disease compared with patients with a normal Lp(a) level and a low content of monocytes. Conclusion: Hyperlipoproteinemia(a) and a decreased quantity of classical monocytes were associated with the severity of coronary atherosclerosis. The expansion of CD16+ monocytes (intermediate and non-classical) in the presence of hyperlipoproteinemia(a) significantly increased the risk of triple-vessel coronary disease.

Lipoprotein(a), Immune Cells and Cardiovascular Outcomes in Patients with Premature Coronary Heart Disease

“…The activation of the innate immune system in patients with hyperlipoproteinemia(a) is consistent with our recent study, which demonstrated that in patients with an elevated Lp(a) concentration, there is a redistribution of monocyte subpopulations towards an increase in CD14+CD16++ monocytes [13]. Furthermore, the combination of hyperlipoproteinemia(a) and a higher content of intermediate monocytes was associated with a significant increase in stenotic plaques in all major coronary arteries.…”

“…There are data that Lp(a) is able to enhance the production of inflammatory monocytes in the bone marrow [12]. We have recently shown that in patients with an elevated Lp(a) level, the absolute and relative content of non-classical CD14+CD16++ monocytes is significantly higher [13], indicating the ability of Lp(a) to influence monocytes. Residual cardiovascular risk in patients with atherosclerosis, despite adequate hypolipidemic therapy, could be related to the increased concentration of Lp(a) and, therefore, the possible relationship between Lp(a) and the vascular wall inflammation deserves further evaluation.…”

Nature versus Number: Monocytes in Cardiovascular Disease

“…Patients with atherosclerosis in multiple vessels had significantly more CD16+ (intermediate + nonclassical) monocytes than those with single vessel disease [24]. This relationship was also seen when patients were divided by proportion of monocyte subsets, with those below median for classicals or above median for intermediate or nonclassicals having a higher occurrence of multivessel disease [25]. In PAD patients, the presence of ischemic ulcer (an indicator of greater disease severity) is associated with decreases in classical monocyte proportion and increases in intermediate monocyte proportion [26].…”

Lipoprotein(a) variations between Chronic Coronary Syndrome and Acute Myocardial Infarction and their relation to the severity of coronary artery stenosis

“…Whereas the development of CAD is a dynamic process [1], little attention has been paid to the changes in Lp(a) levels at different times. One study showed that elevated Lp(a) levels were associated with CD14, CD16 monocyte reduction and coronary atherosclerosis, but the study inclusion population did not include patients with coronary events [12]. In the last decades, coronary heart disease remains the leading cause of death worldwide [13].…”